tbuckley/cabot-search huggingface dataset:
QLTI-05. HBA1C AND INSULIN COVERAGE FOR NEWLY DIAGNOSED HGG PATIENTS IN THE HOSPITAL
Authors: Patrick Regis, Robert Cavaliere
Journal: Neuro-Oncology (2022)

Abstract Corticosteroids are used in the management of patients with high-grade gliomas (HGG). Corticosteroids lead to elevated serum glucose levels, necessitating sliding-scale insulin. A hemoglobin A1c (HbA1c) reflects historical serum glucose levels but it’s unclear if it predicts corticosteroid-induced hyperglycemia. We retrospectively reviewed all newly diagnosed HGG patients who were admitted between Jan 2019 to July 2021 who had an HbA1c performed at the time of their diagnosis. HbA1c is classified into: normal (&amp;lt; 5.6%), elevated (5.7 – 6.4%) and diagnostic (&amp;gt; 6.5%). We identified 86 patients of whom 29 and 16 had elevated and diagnostic HbA1c, respectively. These patients were more likely to require sliding scale insulin at least twice during their hospitalization, 64% vs 13% of those with a normal HbA1c. Only 28% of patients had a history of diabetes. There was no correlation between elevated HbA1c and the likelihood of initiating post-operative therapy, surgical complications, or BMI results. When reviewing age, 39 patients were less than 65, of which 34% had at least an elevated HbA1c. Of those older than 65, 65% had at least an elevated HbA1c. Our analysis suggests there is a predictive value of HbA1c and the need for sliding-scale insulin while receiving corticosteroids in the HGG population, especially in the older population. We recommend screening all new HGG patients with an HbA1c at the time of diagnosis, regardless if they have a history of diabetes. We also recommend monitoring serum glucose less frequently with those who have a normal HbA1c. If the HbA1c is elevated or diagnostic, they should have monitored serum glucose levels with available sliding-scale insulin. If the patient is &amp;gt; 65 years of age, they should be considered a higher risk for having hyperglycemia and HbA1c should be reviewed. Further analysis is being conducted and will be reviewed at a later date.
TMET-27. DEXAMETHASONE-ASSOCIATED GENE EXPRESSION AND METABOLITE MODIFICATIONS IN GLIOMA TISSUE AND CELL CULTURES
Authors: Christoph Trautwein, Laimdota Zizmare, Louise Maise, Hannes Becker, Marco Skardelly, Marcos Tatagiba, Daniel Merk, Bernd J Pichler, Ghazaleh Tabatabai
Journal: Neuro-Oncology (2022)

Abstract Altered metabolism is amongst the hallmarks of cancer including diffuse glioma. We have recently presented a large database with tissue metabolites that are modulated by IDH1 mutation in diffuse glioma. Furthermore, we suggested potential candidate biomarkers for prospective validation that could serve for further refinement of prognostic groups in IDH1-mutated glioma. Glucocorticoids, particularly dexamethasone, are widely used in neuro-oncology and trigger a variety of metabolic effects, e.g. systemic adverse events including steroid-induced diabetes and truncal weight gain. In this subsequent study, we investigated dexamethasone-associated modifications of metabolite profiles in human glioma tissue (n=24 treated with dexamethasone, n=77 without) and in glioma cell lines. We performed ex-vivo Nuclear Magnetic Resonance (NMR) spectroscopy and RNA sequencing to discover comparison-specific metabolites and pathways. Dexamethasone-associated pathways involved increased energy and growth metabolism. Furthermore, we characterized dexamethasone-induced metabolite modulations in glioma cell lines to investigate dexamethasone effects in a rather homogeneous glioma cell population. We investigated the cellular effects of selected significant metabolites in acute cytotoxicity and clonogenic survival assays. Our data provide further insight into dexamethasone-associated metabolic effects in cell lines and tissue that might be relevant for further studies and its use in clinical practice.
RADT-17. A CASE OF RECURRENT GLIOBLASTOMA EFFECTIVELY TREATED WITH TUMOR-TREATING-FIELDS(TTFS)
Authors: Xin Geng, Hongming Ji, Rui Cheng
Journal: Neuro-Oncology (2022)

Abstract The patient was admitted to our hospital due to sudden headache in February 2021, and the head MRI showed "right frontal mass". On February 8, 2021, a large right forehead mass resection was performed under general anesthesia. The postoperative pathology showed: Glioblastoma (WHO grade IV). Regular chemotherapy with temozolomide was given postoperatively. In June 2021, the re-examination of the head MRI examination considered the possibility of recurrence, and tumor-treating-fields(TTFs) was started. Subsequently, the head MRI was reviewed every 2 months, and it was seen that the lesions gradually shrank. At present, the patient is generally in good condition without headache and other discomfort, and has obtained 15 months of PFS since the operation.
BIOM-53. SPECIFIC MICRORNA EXPRESSION PATTERN PREDICTS RECURRENCE IN ATYPICAL MENINGIOMA
Authors: Pavel Fadrus, Dagmar Tukmachi, Milos Duba, Ondrej Naar, Vaclav Vybihal, Jiri Sana, Martin Smrcka, Ondrej Slaby
Journal: Neuro-Oncology (2022)

Abstract Meningiomas are the most common primary tumors of the central nervous system (CNS). Atypical meningioma (AM) recurs in 40% of patients despite total resection and radiotherapy (RT). No consensus on optimal adjuvant management was found, and it is difficult to identify patients insensitive to RT in real-life clinical practice. A promising group of biomarkers represent microRNAs (miRNAs), short non-coding RNAs that regulate most biological processes, including cell proliferation, differentiation, and apoptosis. The study aims to identify tissue miRNAs capable of predicting patients with AM who could benefit from the indicated adjuvant RT. The study includes 80 patients with AM in the exploratory phase and 400 patients with meningioma in the validation phase. Total RNA enriched with miRNAs was isolated from FFPE tissue using the mirVana miRNA Isolation Kit (TF Scientific). Subsequently, RNA quantity and quality controls were measured using NanoDrop 2000 (TF Scientific) and Qubit 2.0 (TF Scientific) instruments. A global miRNA expression profile was generated using the TaqMan Array Human MicroRNA Cards (TF Scientific), which allow the detection of up to 754 miRNAs simultaneously. Obtained data were processed and integrated through bioinformatics algorithms with clinicopathological data of patients with AM.The study identified significantly dysregulated miRNAs among AM patients with and without recurrence (p &amp;lt; 0.05). Results also suggest dysregulated miRNA expression profile in AM patients with indicated RT who did/did not develop a recurrence (p &amp;lt; 0.05). Lists of individual miRNAs and detailed graphical analyses will be included in the conference presentation.The results will help predict the prognosis of surgically intervened patients more accurately and can help determine which patients will benefit from the adjuvant RT. This research is supported by the AZV grant from the Ministry of Health of the Czech Republic (reg. No. NV19-03-00559) and Conceptual development of research organization (FNBr, 65269705). All rights reserved.
INNV-19. THE DETECTION OF DISSEMINATED PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION (PPTID) IN CEREBROSPINAL FLUID (CSF) USING CELL CAPTURE AND IMMUNOCYTOCHEMISTRY
Authors: Kaitlyn Armijo, Nathan Sweed, Steven Hsiao, Tony Pircher, Mikayla Marrin, Leslie Cho, Kelly Kreitzburg, Barbara Blouw, Deanna Fisher, Michael Dugan, Santosh Kesari
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Pineal parenchymal tumors of intermediate differentiation (PPTID) account for 21% to 54% of pineal parenchymal tumors and may be complicated by cerebrospinal dissemination (most commonly at time of reoccurrence; up to 4-10 years post resection). The integral membrane protein synaptophysin is expressed in neuroendocrine cells and virtually all neuraxial neurons that contribute to synaptic transmission. PPTID frequently demonstrates synaptophysin independently of other neural differentiation markers. Cerebrospinal fluid (CSF) cell capture assays have demonstrated utility for assessing disseminated intracranial neoplasms, thus we explore this technology for monitoring a patient with PPTID. METHODS A 30-year-old female patient with PPTID diagnosed two years prior was suspected for intracranial dissemination and underwent five CSF collections over the course of 64 days. Per collection, approximately 7 mL of CSF was submitted for each cytology and cell capture. Cytology was performed at Providence Saint John’s Health Center. The CNSide™ platform (Biocept, Inc.) was used to capture and stain cells for DAPI, synaptophysin, and CD45. Multiple capture antibody cocktails (termed 1986, 1822, and gTP1—originally developed for use in carcinoma, melanoma, and glioma) were tested. Cells of interest (COI) were defined by positive immunoreactivity for both DAPI and synaptophysin and no immunoreactivity for CD45. Results were quantified and compared longitudinally. RESULTS CSF analysis on days 0, 9, 21, 36, and 64 demonstrated negative results by cytology and 51, 96, 170, 130, and 43 COI/mL by the CNSide platform, respectively. Cumulative mean capture rates for cocktails 1986, 1822, and gTP1 were 47, 14, and 36 COI/mL/sample, respectively. DISCUSSION A significant amount of PPTID patients will develop cerebrospinal dissemination. The importance of craniospinal control in this setting has been previously demonstrated. Our work suggests that cell capture assays paired with immunocytochemistry can be used as sensitive means to monitor disseminated PPTID and may impact treatment decisions.
ANGI-09. BEVACIZUMAB IN ATYPICAL AND ANAPLASTIC MENINGIOMAS: THE BEMEN STUDY
Authors: Giulia Cerretti, Alberto Bosio, Marta Maccari, Marta Padovan, Mario Caccese, Vittorina Zagonel, Giuseppe Lombardi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND the current standard to treat meningiomas can include surgical resection and radiotherapy. Despite the high rate of relapse no systemic treatment is indicated. Few data are available regarding the effectiveness of bevacizumab (BEV) in this setting. We performed a retrospective analysis investigating the efficacy and safety of BEV in meningioma patients relapsed after receiving surgery and radiotherapy. Gene mutations were also collected. Material and METHODS we analyzed pts treated with off-label BEV from Jul 2019 to Feb 2022. Inclusion criteria were diagnosis of grade 2-3 meningioma, previous treatment with surgery and radiotherapy, no indication to further surgery or reirradiation, absence of contraindications to the use of BEV. Data were estrapolated from clinical records. RESULTS Median follow up was 13 months (3-30 range). 26 pts were enrolled. Median age was 68 ys (29-84); male pts were 16 (61%);61% (16 pts) with atypical meningioma, 38.5% (10 pts) with anaplastic meningioma; 27% (7 pts) underwent 2 or more surgeries; 58% had 2 or more RT treatments; 96.1% (25 pts) received &amp;lt; 2 previous lines of systemic treatment. 61% of patients (16 pts) had NGS analyses available; 62% (10 pts) had NF2 mutations (1 pt had a confirmed diagnosis of neurofibromatosis type 2), 23% (6 pts) CDKN2A/2B deletion, 11% (3 pts) PTEN mutation. OS rate was 82% and 62% at 6 and 12 months respectively; 6 months PFS rate was 83%. The DCR was 71% and the ORR was 19%. Median PFS and OS weren't reached. 19% (5 pts) experienced CTCAE grade 1 or 2 toxicity, mainly hypertension. CONCLUSION BEV showed very promising activity in recurrent grade 2-3 meningioma. The treatment was well tolerated. BEV should be considered an optimal therapeutic option in this setting of meningioma patients. The NGS results might be useful in identifying targetable mutations in case of further recurrence.
NIMG-95. IMAGING CHARACTERISTICS OF POLYMORPHOUS LOW GRADE NEUROEPITHELIAL TUMOR (PLNTY)
Authors: Camille Gordon, Javier Quintana, Ignacio Gonzalez-Gomez
Journal: Neuro-Oncology (2022)

Abstract Polymorphous low grade neuroepithelial tumor of the young (PLNTY) was first described in 2017 in the pathology literature based on the unique histologic and molecular characteristics. Most of the patients in the original article presented with seizures linked to a temporal lobe lesion. We report a pediatric patient who presented with seizures found to have a lesion which was consistent with PLNTY on biopsy. We will review the radiology and pathology of this case with a quick review of the characteristic findings of PLNTY.
CNSC-27. AN IDO-PROTAC HIGHLIGHTS A NOVEL TRYPTOPHAN METABOLISM- INDEPENDENT ROLE FOR IMMUNOSUPPRESSIVE IDO IN HUMAN GLIOBLASTOMA
Authors: Prashant Bommi, Paige Monsen, Lakshmi Bommi, Lijie Zhai, April Bell, Kristen Lauing, Xinlei Mi, Masha Kocherginski, Craig Horbinski, Rimas Lukas, Gary Schiltz, Derek Wainwright
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO) is an immunosuppressive enzyme that catabolizes the essential amino acid, tryptophan (Trp), into the metabolite, kynurenine. IDO is expressed in &amp;gt;90% of patient resected GBM. IDO suppresses the anti-brain tumor immune response, in-part, through non-metabolic activities. To determine how IDO non-metabolically suppresses the anti-GBM immune response, IDO-protein degrader (IDO-proteolysis targeting chimera; IDO-PROTAC) effects were studied in multiple human models of GBM. METHODS The IDO-expressing GBM cell lines, U87, U138, as well as the patient derived xenograft (PDX) line, GBM43, were treated with either IDO-PROTAC, mutant PROTAC, IDO enzyme inhibitor, or IDO siRNA, followed by RNA-seq analysis and/or mass spectrometry with quantitative proteomics using tandem mass tag (TMT) labelling. RESULTS Transcriptomic analysis revealed differentially expressed genes that were commonly regulated after treatment with the IDO-PROTAC as compared to treatment with the mutant PROTAC or IDO enzyme inhibitor groups in U87, U138, and GBM43 cells. Mass spectrometry analysis found 34 unique proteins that were differentially expressed inside of human GBM cells, with an additional 20 unique proteins that were identified in the supernatant of cultured human GBM cells after IDO-PROTAC treatment. Meta-analysis of the transcriptomic and proteomic analyses identified a novel factor that was unique to IDO-PROTAC treatment. GO terms that were enriched after IDO-PROTAC treatment identified nucleoside kinase activity as well as metallocarboxypeptidase activity. CONCLUSIONS This study discovered multiple new targets and pathways that immunosuppressive IDO regulates through a non-metabolic function. Functional analyses that validate the newly-discovered IDO-dependent, IDO-enzyme independent factors, are ongoing.
STEM-19. LIVE DETECTION OF NEURAL STEM AND GLIOBLASTOMA CELLS BY A LUMINESCENT CONJUGATED OLIGOTHIOPHENE DERIVATIVE
Authors: Shirin Ilkhanizadeh, Aileen Gracias, Andreas K O Åslund, Marcus Bäck, Rozalyn Simon, Christina Neofytou, Vilma Rraklli, Bianca Migliori, Edel Kavanagh, Sven Nelander, Bengt Westermark, Lene Uhrbom, Karin Forsberg-Nilsson, Ana I Teixeira, Peter Konradsson, Per Uhlén, Johan Holmberg, Bertrand Joseph, K Peter R Nilsson, Ola Hermanson
Journal: Neuro-Oncology (2022)

Abstract Glioblastoma (GBM) is an aggressive nervous system tumor with a mean survival time of 12-14 months. Cells with neural stem cell-like properties can be derived from GBM tumors. These cells seem to escape conventional irradiation treatment, chemotherapy, and surgery, and may play a crucial role for relapse. It is therefore urgent to develop novel approaches for reliable detection of neural stem cell-like cells in GBM. Here we report a luminescent conjugated oligothiophene (LCO), named GlioStem (p-HTMI), for non-invasive and non-amplified real-time detection of live human patient-derived GBM cells and embryonic neural stem/progenitor cells (NSPCs). Within a maximum of 10 minutes after administration of the molecule in vitro, in the existing media, fluorescence emission was observed without any modulation of the cells or additional vehicle, resulting in efficient detection of cytoplasmic luminescent signal in NSPCs or GBM cells from rodents and humans, detectable at Alexa488/GFP wavelength. GlioStem is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. In vitro, GlioStem was shown to identify fetal cortical NSPCs from rat (FGF2-expanded), embryonic stem cell-derived NSPCs from mouse (FGF2/EGF-expanded), and FGF2-exposed C6 glioma cell cultures from rat, but not any other cell types investigated. Cell sorting experiments of patient-derived, FGF2/EGF-expanded GBM cells demonstrated that GlioStem in addition to NSPC-markers like Nestin and Sox2 labeled the same population (overlap &amp;gt; 90%) of cells as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO GlioStem is a versatile tool for immediate and selective detection of subpopulations of neural stem and glioma cells.
CSIG-38. ENGINEERED PULLULAN-COLLAGEN-GOLD NANO COMPOSITE IMPROVES MESENCHYMAL STEM CELLS NEURAL DIFFERENTIATION AND INFLAMMATORY REGULATION
Authors: Tracy Chen, Meng-Yin Yang
Journal: Neuro-Oncology (2022)

Abstract Tissue repair engineering supported by nanoparticles and stem cells is an efficient strategy for promoting the healing potential of damaged tissues. Tissue repair engineering supported by nanoparticles and stem cells is an efficient strategy for promoting the healing potential of damaged tissues. In this study, we prepared various nanomaterials including pure Pul, pure Col, Pul–Col, Pul–Au, Pul–Col–Au, and Col–Au to investigate their physicochemical properties, biocompatibility, biological functions, differentiation capacities, and anti-inflammatory abilities through in vitro and in vivo assessments. The physicochemical properties were characterized by SEM, DLS assay, contact angle measurements, UV-Vis spectra, FTIR spectra, SERS, and XPS analysis. Pul–Col–Au composite enhanced cell viability, promoted anti-oxidative ability for MSCs and HSFs, inhibited monocyte and platelet activation, induced the lowest cell apoptosis, facilitated the MMP activities and improved endothelialization. In conclusion, Pul–Col–Au nanoparticles are promising material for tissue regeneration.
NIMG-97. A FULLY AUTOMATED MRI-BASED DEEP-LEARNING ALGORITHM FOR CLASSIFYING GERMINOMAS AND NONGERMINOMATOUS GERM CELL TUMORS
Authors: Yanong Li, Xiaoguang Qiu
Journal: Neuro-Oncology (2022)

Abstract Intra-cranial germ cell tumors (iGCTs) are classified into two pathological subtypes Germinomas (GEs) and nongerminomatous germ cell tumors (NGGCTs). Accurate preoperative determination of iGCT subtypes is essential to guide clinical decision making and prognosis assessment. This study aims to develop a deep-learning algorithm to automatically segment iGCTs and classify subtypes using preoperative T2-weighted (T2W) images. Brain MR imaging and corresponding pathologic information were retrospectively obtained from 594 subjects including 269 GEs and 325 NGGCTs from Beijing Tiantan Hospital between January 1, 2008, and October 31, 2020, and subdivided into training (n=416) and test (n=178) sets for iGCTs segmentation, and classification using 3D nnU-Net based on T2W images. An internal validation cohort (including 56 GEs and 17 NGGCTs) and two external validation cohorts (Center 1 including 13 GEs and 12 NGGCTs；Center 2 including 17 GEs and 12 NGGCTs) were prospectively designed as an independent sets for testing the iGCT-net. Dice scores were computed to assess tumor segmentation. Accuracy and area under the curve (AUC) were calculated to assess the GEs and NGGCTs classification. Additionally, sensitivity analysis of different tumor location (suprasellar, pineal and basal ganglia regions) was performed to access the classification accuracy. The iGCT-net for tumor segmentation achieved a mean dice score of 0.80 in all cohorts. For tumor classification, the iGCT-net achieved the mean accuracy of 90.96% of all cohorts, which was superior to that using demographics and morphologic features (mean = 67.50%, p&amp;lt; 0.01). For different tumor location (suprasellar region, pineal region, and basal ganglia region), the iGCT-net showed an mean accuracy of 87.94%, 89.38% and 65.74% in test set, internal validation set and external validation cohorts. A fully automatic deep learning algorithm to segment iGCT and discriminate GEs and NGGCTs with high accuracy based on only T2W images from a large dataset is successfully developed.
QOL-08. PHASE II RANDOMIZED STUDY TO EVALUATE EFFICACY AND SATISFACTION OF ROLAPITANT PLUS ONDANSETRON VS. ONDANSETRON MONOTHERAPY IN PREVENTING NAUSEA/VOMITING FOR GLIOMAS RECEIVING RADIATION/TEMOZOLOMIDE
Authors: Mary Lou Affronti, Mallika Patel, Erin Severance, Charles Loughlin, Claire Bradbury, James E Herndon, Kendra Boyd, Eric S Lipp, Henry S Friedman, Annick Desjardins, Margaret Johnson, Katherine B Peters
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Nausea and vomiting remain the most feared cancer treatment-related side effects. Trials establishing antiemetic guidelines exclude malignant glioma (MG) patients. In MG patients receiving radiation with concurrent temozolomide, chemoradiation-induced nausea and vomiting (cRINV) rates are 35 and 26%, respectively, which reduce quality of life, treatment adherence, and potentially cancer control.OBJECTIVES: In a randomized phase II open label trial, we compared patient satisfaction and efficacy of ondansetron monotherapy (short-acting 5HT3-RA; 3h half-life) vs. rolapitant (long-acting NK1-RA; 180h half-life) plus ondansetron in preventing cRINV during 6-weeks of daily temozolomide (75 mg/m2/dX42d) with radiation. METHODS Fifty-three eligible patients receiving chemoradiation were randomized to Arm-A (ondansetron 8mg Days 1-42, rolapitant 180mg on Day 21) or Arm-B (rolapitant on Day 1 plus daily ondansetron). Primary endpoint included the percentage achieving cRINV-complete response (CR; no vomiting or antiemetic rescue) during the first 2-weeks of radiation. Secondary endpoints included cRIN/cRIV rates, preference for rolapitant plus ondansetron, and toxicity. RESULTS Forty-eight initiated protocol treatment. Mean age=53, 58% male, median KPS 90%, 71% low alcohol N/V risk factor, 73% glioblastoma. During the first 2-weeks of radiation, cRINV-CR was 60% for 25 evaluable patients receiving ondansetron monotherapy and 65% for 23 receiving rolapitant/ondansetron (p&amp;lt; 0.71). Patient-reported cRINV-CR was 61% and 74%, respectively (p&amp;lt; 0.41); cRIN rates (44% Arm-A; 53% Arm-B) were more than cRIV rates (28% Arm-A; 11% Arm-B). More patients receiving ondansetron alone vomited the first 2-weeks (22%) than with rolapitant/ondansetron (0%); p&amp;lt; 0.05. Among 32 patients who completed the study, patients preferred ondansetron (63%) over rolapitant/ondansetron (19%); p&amp;lt; 0.0039; 19% had no preference. Adverse events attributable to antiemetic treatment (fatigue/constipation) were all grade 1-2. CONCLUSIONS While patients prefer ondansetron monotherapy, there was no difference in cRINV-CR between the first 2-week treatments and some had less vomiting with rolapitant plus ondansetron. We will present overall N/V results.